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Flying into Hobby, 5pm Monday, one night in Houston...next day visiting Space Centre, then straight on to San Antonio...so, my question is, would people book hotel between Airport and Space Centre, or drive into city centre for the night? We would like to be able to walk from hotel area for a few beers and finish with some Texas bbq.

No need to go to the city center (downtown). Stay the night in Kemah - Kemah Boardwalk Inn is a good option. There is also a HI, some B&B and other options. Several places to eat / drink within walking distance. One thing though, you are not going to find the best BBQ within the boardwalk. Never been to this place - but have herad that T.Bone Tom's has really good BBQ - about 1/2 mile from the boardwalk. So maybe drive to it, have dinner and then drinks along the boardwalk. Kemah is also close to NASA.

From there it is a straight shot along 45 to I-10 (West) that will take you to San Antonio.

A further suggestion for consideration. While I'm not a fan of Landry's restaurants in general, they have decent seafood, so stay near Kemah boardwalk and eat seafood. Then, after you've visited Nasa, on your way to San Antonio, stop in Luling (right on I-10) and eat at Luling City Market, which is far better than anything than anything you'll get in the Kemah/Nasa neighborhood. If you are interested in going 30 miles out of the way, you could head up to Lockhart, but based on my personal experience at Black's BBQ, I wouldn't go out of the way to try any of the "famous" BBQ places there--Luling is fine, and about 2-2.5 hours west of Houston.